Biological Sciences Division Research Highlights

May 2014

Study Breathes Understanding into Plutonium-Nitrate Effects

Team examines human, dog tissues to expand knowledge of exposure and retention outcomes

An autoradiograph of a human subject’s respiratory tissue shows alpha star aggregate of plutonium, localized within connective tissue along the pleura membrane that covers the lung. Other black material in the image is cigarette residue. Enlarge Image.

Results:
A study led by Pacific Northwest National Laboratory (PNNL) scientists
offers new insights into the retention of plutonium-nitrate in the lungs-as
well as clues as to the cellular processes and structural changes that might
lead to tissue damage and tumor formation.

In this unique inquiry, researchers from PNNL, Battelle
Toxicology Northwest, and the United States Transuranium and Uranium Registries
(USTUR) at Washington State University prepared, analyzed, and compared
archived tissue samples from a deceased nuclear worker and beagle dogs. All of
the subjects had inhaled plutonium. The research team sought to better
understand what happens after plutonium-nitrate, a moderately soluble form of
plutonium, is inhaled, deposited in the lungs, and retained.

In both the human and
beagles, there were statistically significant modifications in the expression
of three regulatory proteins-Fas ligand (FASLG), B-cell lymphoma 2 (BCL2), and
Caspase 3 (CASP3). FASLG influences the immune system and cancer progression;
BCL2 regulates apoptosis, or cell death; and CASP3 also plays a role in
apoptosis. The research findings suggest that these proteins, as well as
apoptosis, are central in coordinating the body's responses to the long-term
presence of plutonium-nitrate in the lungs.

Why
It Matters: While much is known about plutonium from biological,
radiological, and toxicokinetic perspectives, there is not yet a clear
understanding of the specific mechanisms by which ionizing radiation produces
its effects or about the resulting long-term health consequences.

The PNNL-led research sought to investigate whether
plutonium retention produces elevated levels of cell death and to test the
hypothesis that plutonium exposure results in alterations of expression
profiles of selected factors. The study adds to the body of fundamental
knowledge regarding lung morphology and gene expression modifications.

"The methods used here
undoubtedly will extend to future research, building upon the advances of this
project," says Dr. William Morgan, a PNNL radiation biologist and member of the
research team.

Methods:
The carcinogenic and inflammatory effects of plutonium-nitrate retention were
examined from a human and large animal perspective. The project obtained tissue
from a deceased nuclear worker who had accidentally inhaled plutonium
approximately 38 years before his death. Tissue from another deceased nuclear
worker served as a control. Both individuals had donated their bodies to
science, and the tissue samples were stored at USTUR in light-sealed containers
and maintained at a constant and appropriate temperature. The study also
included tissues from 15 beagle dogs. The dogs were subjected to inhalation
exposure of plutonium-nitrate as part of a 1970s study that continued for more
than a decade.

Sponsors:
The work was funded by
the Laboratory Directed Research Development program at PNNL. Subsequent
funding was provided by the U.S. Department of Energy's Office of Biological
and Environmental Research Low Dose Radiation Research Program, the Fred
Hutchinson Cancer Research Center, the National Institutes of Health's National
Institute for Allergy and Infectious Disease, and the Center for Medical
Countermeasures against Radiation.